BIOMARKERS OF EXPOSURE AND EFFECT IN A TRAFFIC EXPOSED POPULATION

描述（由申请人提供）：可归因于交通和其他燃烧源的颗粒物（PM）与心脏相关的健康结果、呼吸系统疾病、肺癌和总体死亡率有关。动物和人类的实验证据表明，暴露于交通相关的PM会导致全身炎症、氧化应激和细胞周期失调，以及直接的遗传毒性。然而，精确的机制定义不清，并且没有在“现实世界”的大型人群中得到很好的表征。我们建议在卡车运输业颗粒研究（一项正在进行的国家流行病学和暴露评估研究）的亚人群中收集重复的血液和尿液样本，同时前瞻性地描述个人暴露于汽车尾气的特征。我们将评估测量暴露与暴露的生物标志物以及氧化和炎症效应之间的关系。具体来说，我们将测量1,2萘醌和1,4萘醌白蛋白加合物和尿萘酚（交通相关暴露的生物标志物）的血清水平，以及c反应蛋白、白细胞介素-6和可溶性细胞间粘附分子-1的血清水平，以及8-羟基-2'-脱氧鸟苷（生物效应标志物）的尿水平。暴露测量将包括元素碳、萘和结合的多环芳烃（PAH），这是一种附着在元素碳颗粒上的多环芳烃的新型特异性指标，可以将它们浓缩并运输到肺部和内脏的目标区域。最后，我们将使用全血RNA进行全基因组基因表达微阵列分析，以识别在汽车尾气暴露反应中差异激活的基因和基因网络。我们预计，这个项目的结果将提供新的和全面的见解，正常的生物反应对汽车尾气，相关的致病因素暴露，并将进一步我们的理解这些过程涉及到肺癌和心脏病的发展。这些问题具有重大的公共卫生重要性，因为大部分普通人口每天都暴露在汽车尾气中。此外，我们提出的目标与NIEHS环境基因组计划（EGP）的目标一致，即提高对人类对环境暴露的遗传易感性的理解。公共卫生相关性：可归因于交通和其他燃烧源的颗粒物（PM）与心脏相关的健康结果、呼吸系统疾病、肺癌和总体死亡率有关。我们预计，这个项目的结果将提供新的和全面的见解，正常的生物反应对汽车尾气，相关的致病因素暴露，并将进一步我们的理解这些过程涉及到肺癌和心脏病的发展。这些问题具有重大的公共卫生重要性，因为大部分普通人口每天都暴露在汽车尾气中。

DESCRIPTION (provided by applicant): Particulate matter (PM) attributable to traffic and other combustion sources has been associated with cardiac- related health outcomes, respiratory disease, lung cancer, and overall mortality. Experimental evidence in animals and humans suggests that exposure to traffic-related PM results in systemic inflammation, oxidative stress and cell cycle dysregulation, as well as direct genotoxicity. However, the precise mechanisms are poorly defined and have not been well characterized in large "real-world" populations. We propose to prospectively characterize personal exposures to vehicle exhaust while concurrently collecting repeated blood and urine samples in a subpopulation of the Trucking Industry Particle Study, an ongoing national epidemiologic and exposure assessment study. We will assess relationships between measured exposures and biomarkers of exposure and oxidative and inflammatory effects. Specifically we will measure serum levels of 1, 2 naphthoquinone and 1, 4-naphthoquinone albumin adducts and urinary naphthols (biomarkers of traffic- related exposure) and serum levels of C-reactive protein, interleukin-6 and soluble intercellular adhesion molecule-1 and urine levels of 8-hydroxy-2'-deoxyguanosine (biomarkers of effect) with concurrent exposure measurements. Exposure measurements will include elemental carbon, naphthalene, and bound polycyclic aromatic hydrocarbons (PAH), a novel specific indicator of PAHs attached to elemental carbon particles that can concentrate and transport them into the target areas of the lungs and internal organs. Finally, we will perform genome-wide gene expression micro array analysis using whole blood RNA to identify genes and gene networks that are differentially activated in response to vehicle exhaust exposure. We anticipate that the results of this project will provide novel and comprehensive insights into the normal biologic response to vehicle exhaust, the relevant etiologic agents of exposure, and will further our understanding of those processes implicated in the development of lung cancer and heart disease. These issues are of great public health importance due to the large proportion of the general population exposed to vehicle exhaust on a daily basis. Furthermore, our proposed aims are consistent with the goals of NIEHS Environmental Genome Project (EGP) to improve understanding of human genetic susceptibility to environmental exposures PUBLIC HEALTH RELEVANCE: Particulate matter (PM) attributable to traffic and other combustion sources has been associated with cardiac- related health outcomes, respiratory disease, lung cancer, and overall mortality. We anticipate that the results of this project will provide novel and comprehensive insights into the normal biologic response to vehicle exhaust, the relevant etiologic agents of exposure, and will further our understanding of those processes implicated in the development of lung cancer and heart disease. These issues are of great public health importance due to the large proportion of the general population exposed to vehicle exhaust on a daily basis.